With the EC marketing authorization, Zeposia, an oral medication taken once daily, becomes the only approved sphingosine-1-phosphate (S1P) receptor modulator for RRMS patients with active disease. The approval is based on data from the SUNBEAM and RADIANCE Part B clinical trials showing that, as compared to AVONEX (interferon beta-1a), Zeposia delivered powerful efficacy as measured by annualized relapse rate (ARR), as well as on the number and size of brain lesions.
“Today’s European Commission approval provides the opportunity for patients with RRMS with active disease to be offered Zeposia as a new first-line treatment option, which is an important advancement based on Phase 3 trial results showing significant improvements in relapses and brain lesions caused by this devastating disease,” said Samit Hirawat, M.D., chief medical officer, Bristol Myers Squibb. “We share this achievement with the courageous multiple sclerosis patient community in Europe and around the globe, and are working closely with all stakeholders to ensure that eligible European patients can start benefitting from Zeposia as quickly as possible.”
Multiple sclerosis (MS) is a disease in which the immune system attacks the protective myelin sheath that covers the nerves, creating damaging lesions that make it harder for signals to travel between each nerve cell. This “signal breakdown” can lead to symptoms and relapses.
The approval was based on data from the randomized, active-controlled Phase 3 SUNBEAM and RADIANCE Part B clinical trials, which enrolled more than 2,600 patients across 150 sites in more than 20 countries. Key findings from the trials include:
- Zeposia demonstrated a relative reduction in ARR versus AVONEX of 48% through one year in the SUNBEAM study and 38% at two years in the RADIANCE study (absolute ARR of 0.18 versus 0.35 and 0.17 versus 0.28, respectively).
- At one year in the SUNBEAM study, treatment with Zeposia reduced the number of T1‑weighted gadolinium-enhanced (GdE) brain lesions more than AVONEX (0.16 vs 0.43), a relative reduction of 63%, and reduced the number of new or enlarging T2 brain lesions (1.47 versus 2.84), a relative reduction of 48%.
- At two years in the RADIANCE study, treatment with Zeposia reduced the number of T1‑weighted GdE brain lesions more than AVONEX (0.18 versus 0.37), a relative reduction of 53%. Zeposia also reduced the number of new or enlarging T2 lesions versus AVONEX (1.84 versus 3.18), a relative reduction of 42%.
- Zeposia demonstrated a reduction in percent change from baseline in whole brain volume as compared to AVONEX at one year in the SUNBEAM study (-0.41% versus -0.61%) and at two years in the RADIANCE study (-0.71% versus -0.94%).
“There is no one-size-fits-all approach to treating MS. Patients respond differently to currently available therapies, which is why having options that address the hallmark characteristics of RRMS is so important,” said Giancarlo Comi, M.D., Honorary Professor of Neurology, Director of the Institute of Experimental Neurology at the Vita-Salute San Raffaele University in Milan. “Given its demonstrated efficacy and safety profile, Zeposia represents an important new treatment option that I am excited to offer my patients.”
Zeposia is the only approved S1P receptor modulator that offers RRMS patients with active disease an initiation with no first-dose observation required for the majority of patients.1 First-dose monitoring is only recommended for high-risk patients with certain pre-existing cardiac conditions. A dose escalation regimen from day 1 to day 7 should be used to reach the maintenance dose of Zeposia, as a transient decrease in heart rate and atrioventricular conduction delays may occur.
Zeposia demonstrated manageable safety and tolerability in the Phase 3 SUNBEAM and RADIANCE Part B trials. Zeposia is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients, as listed in the Summary of Product Characteristics (SmPC); immunodeficient state; patients who in the last six months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization or New York Heart Association (NYHA) Class III/IV heart failure; patients with history or presence of second-degree atrioventricular (AV) block Type II or third-degree AV block or sick sinus syndrome unless the patient has a functioning pacemaker; severe active infections, active chronic infections such as hepatitis and tuberculosis; active malignancies; severe hepatic impairment (Child-Pugh class C); and during pregnancy and in women of childbearing potential not using effective contraception. Zeposia is associated with the following Special Warnings and Precautions for Use: bradyarrhythmia, liver injury, immunosuppressive effects, increased risk of infections, progressive multifocal leukoencephalopathy, cutaneous neoplasms, macular oedema, posterior reversible encephalopathy syndrome, increased blood pressure, respiratory effects and severe increase in disability after stopping Zeposia. The most common adverse reactions (incidence ≥4%) were upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain and hypertension.
“Multiple sclerosis is an unpredictable and often disabling disease that affects about 700,000 people in Europe. We are delighted by the news that there is now another treatment option available to potentially delay the progression of this debilitating disease,” said Pedro Carrascal, President of the European Multiple Sclerosis Platform.
Source: Company Press Release